Enhance therapeutic efficacy of BiTE (HER2/CD3) for HER2- positive tumors through in vivo expression

Bispecific T-cell engagers (BiTEs) are small-molecule antibodies that exhibits potent tumoricidal activity but suffer from a short plasma half-life. Mesenchymal stromal cells (MSCs) represent promising delivery vehicles for sustained therapeutic protein expression. In this study, we used human umbilical cord blood-MSCs (hUC-MSCs) as a delivery system to to secrete HER2/CD3 BiTE antibodies, thereby addressing the pharmacokinetic limitations of conventional BiTE therapies. HER2 amplification and overexpression are observed in multiple solid tumors, making it a potent target for anti-cancer therapies. Therefore, we constructed a BiTE targeting HER2 and CD3 as a model. In vitro efficacy, both MSCs and MSC-BiTE supernatants could induce significant cell death in BT474 and NCIN87 cells. In vivo, MSC-BiTE inhibited tumor growth in NCIN87 xenograft model. Furthermore, MSC-BiTE elevated the plasma levels of BiTE (HER2/CD3) antibody. Therefore, MSC-BiTE may be used as an efficient therapeutic agent for HER2-positive cancers.